Drug discovery and development is an expensive, time-consuming, and risky enterprise. In order to accelerate the drug development process with reduced risk of failure and relatively lower costs, pharmaceutical companies have adopted drug repositioning as an alternative. This strategy involves exploration of drugs that have already been approved for treatment of other diseases and/or whose targets have already been discovered. Various techniques including data mining, bioinformatics, and usage of novel screening platforms have been used for identification and screening of potential repositioning candidates. However, challenges in clinical trials and intellectual property issues may be encountered during the repositioning process. Nevertheless, such initiatives not only add value to the portfolio of pharmaceutical companies but also provide an opportunity for academia and government laboratories to develop new and innovative uses of existing drugs for infectious and neglected diseases, especially in emerging countries like India.

Background : Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare immune-mediated severe cutaneous adverse reactions with incidence rate of 0.05 to 2 persons per million populations per year. Drugs are the most commonly implicated in 95% of cases. Aims : To audit the causative drugs, clinical outcome, and cost of management in SJS, TEN, and SJS-TEN overlap. Setting and Design: Tertiary care hospitals-based multicentric retrospective study (case series). Materials and Methods : Indoor case papers of SJS, TEN, and SJS-TEN overlap admitted between January 2006 and December 2009 in four tertiary care hospitals of Gujarat were scrutinized. Data were collected for demographic information, causative drugs, investigations, treatment given, duration of hospital stay, time interval between onset of symptoms and drug intake, clinical outcome, and complications. Data were analyzed to find out proportion of individual drugs responsible, major complications, and clinical outcome in SJS, TEN, and SJS-TEN overlap. Total cost of management was calculated by using cost of drugs, investigations, and consumables used during entire hospital stay. Statistical Analysis : One-way Analysis of Variance followed by Tukey-Kramer multiple comparison test was used for comparison of incubation period, duration of hospital stay, and cost of management. Results : Antimicrobials (50%), nonsteroidal anti-inflammatory drugs (22.41%), and antiseizure drugs (18.96%) were the most commonly associated groups. Nevirapine (28.12%) was the most common drug. Antiseizure drugs were more often associated with serious form of adverse reaction (TEN: 81.8%) than other drugs. Duration of hospital stay (20.6 vs 9.7 days) and cost of management (Rs 7 910/- vs Rs 2 460/-) were significantly higher in TEN than SJS (P=0.020 and P<0.001, respectively). Time duration between drug intake and onset of symptoms (17.7 vs 27.5 days) was nonsignificantly lower in TEN as compared with SJS. Secondary infection (28.12%) was the most common complication noted. Mortality rate was 15.6% among all cases; 9% in SJS and 26.7% in TEN. Conclusion : Antimicrobial drugs are the most commonly implicated drugs and cost of managing these adverse drug reactions is higher than other serious ADRs.

A meta-analysis of low-dose aspirin for prevention of preeclampsiaNA TrivediApril-June 2011, 57(2):91-95DOI:10.4103/0022-3859.81858 PMID:21654128

Background : Low-dose aspirin (LDA) is widely used for prevention of preeclampsia. However, conflicting results have been obtained from various studies. Aim: The aim of our study was to evaluate the effect of LDA in prevention of preeclampsia in high-risk and low-risk women. Materials and Methods : A total of 19 randomized control trials were identified using PUBMED search engine and Cochrane Clinical Trial register. The study population was divided into high-risk and low-risk groups. The effect measured was incidence of preeclampsia in women taking either LDA or placebo where the relative risk (RR) and the 95% confidence interval (CI) were calculated for both groups. Results : A total of 28237 women were studied, out of which 16550 were in the low-risk group while 11687 were in the high-risk group. The overall incidence of preeclampsia was 7.4%. With the aspirin group it was 6.9% while in the placebo group it was 7.8%. In the high-risk group there was 21% reduction in the risk of preeclampsia associated with the use of aspirin (RR 0.79, 95% CI 0.65-0.97). However, LDA is not effective in reducing the risk in low-risk population (RR 0.86, 95% CI 0.64-1.17). Conclusion: LDA has a small effect in the prevention of preeclampsia in women considered to be at high risk for the disease. However, it is not effective in reducing the risk in the low-risk group.

Obstructive sleep apnea (OSA) has long been recognized as a disorder characterized by snoring and frequent cessations of breathing resulting in fragmentation of sleep, which eventually leads to cumulative sleep debt in affected patients. Until two decades ago, snoring and apneas drew attention mainly as a social curiosity and sleep apnea was not thought of as a serious disorder with multisystem involvement. Impairment of quality of work and high incidence of motor vehicle accidents associated with OSA were recognized toward the end of the last century. Since the turn of this millennium physicians have become increasingly aware of the various cardiovascular complications, metabolic disturbances, and neuropsychologic deficits. It has become very clear in the last decade that patients with OSA have a high recurrence of atrial fibrillation after elective cardioversion if their sleep apnea is not treated with continuous positive airway pressure (CPAP). Poor control of diabetes mellitus and resistant hypertension in the setting of OSA has also been recognized and significant progress in our understanding in this area has been accomplished. Unless physicians include sleep in their system review, many cases will go undiagnosed, which will eventually result in cardiovascular complications. Patients are also not readily forthcoming with the symptoms of sleep apnea, as they often assume that symptoms, such as snoring and daytime sleepiness, are not something serious to be discussed with their physician. In this review, the characteristics, the pathophysiology, and epidemiology of OSA are discussed. Furthermore, the mechanisms by which OSA affects the cardiovascular, endocrine, and metabolic functions have been explored.

Nonvariceal upper gastrointestinal bleeding is unique from variceal bleeding in terms of patient characteristics, management, rebleeding rates, and prognosis, and should be managed differently. The majority of nonvariceal upper gastrointestinal bleeds will not rebleed once treated successfully. The incidence is 80 to 90% of all upper gastrointestinal bleeds and the mortality is between 5 to 10%. The causes include nonacid-related ulceration from tumors, infections, inflammatory disease, Mallory-Weiss tears, erosions, esophagitis, dieulafoy lesions, angiodysplasias, gastric antral vascular ectasia, and portal hypertensive gastropathy. Rarer causes include hemobilia, hemosuccus pancreaticus, and aortoenteric fistulas. Hematemesis and melena are the key features of bleeding from the upper gastrointestinal tract, but fresh per rectal bleeding may be present in a rapidly bleeding lesion. Resuscitation and stabilization before endoscopy leads to improved outcomes. Fluid resuscitation is essential to avoid hypotension. Though widely practiced, there is currently insufficient evidence to show that routine red cell transfusion is beneficial. Coagulopathy requires correction, but the optimal international normalized ratio has not been determined yet. Risk stratification scores such as the Rockall and Glasgow-Blatchford scores are useful to predict rebleeding, mortality, and to determine the urgency of endoscopy. Evidence suggests that high-dose proton pump inhibitors (PPI) should be given as an infusion before endoscopy. If patients are intolerant of PPIs, histamine-2 receptor antagonists can be given, although their acid suppression is inferior. Endoscopic therapy includes thermal methods such as coaptive coagulation, argon plasma coagulation, and hemostatic clips. Four quadrant epinephrine injections combined with either thermal therapy or clipping reduces mortality. In hypoxic patients, endoscopy masks allow high-flow oxygen during upper gastrointestinal endoscopy. The risk of rebleeding reduces after 72 hours. In rebleeding, repeat endoscopy is useful and persistent failure of endoscopic therapy mandates either embolization or surgery. In this review, we analyze the management of nonvariceal upper gastrointestinal bleeding with evidence from the currently published clinical trials.

Background : Indications for surgery in Hashimoto's thyroiditis (HT) patients are compressive symptoms and suspicion of malignancy. A high incidence of thyroid malignancy has been reported in patients with HT. The effect of surgery on discomfort in swallowing and tightness in the neck has not been properly evaluated. Aims: The aim of our study is to compare the indications, complications, and associated cancers in patients operated for HT with those surgically treated for other benign goitres. The effect of surgery on minor symptoms like tightness in the neck and discomfort in swallowing is included. Setting and Design : This was a retrospective case-control study at a tertiary care centre. Patients and Methods : A total of 271 patients who had undergone surgery for benign thyroid diseases were included. Group A consisted of 35 patients who had HT and Group B consisted of patients operated for other benign thyroid diseases (236 patients). Statistical Analysis : Data were analyzed using SPSS 12 software. Independent group's t-test was used to compare the means and Fisher's exact test was used for categorical data. Results : In Group A, the common indications for surgery were discomfort associated with swelling (45.7%), cosmesis (34.3%), and pain with swelling (11.4%) whereas in Group B, the indication was predominantly cosmetic (80%). A total of 22.9% patients of Group A and 6% of Group B were hyperthyroid. The sensitivity of FNAC for diagnosing thyroiditis was 62.8% (n = 22). Postoperative complication rates were similar in both the groups. The mean operating time was higher in Group A even though the gland was smaller. Incidental malignancy was 3.4% in Group B whereas there was none in Group A. Discomfort in swallowing and tightness in the neck were relieved at 3 months after surgery. Conclusions : Large, euthyroid and apparently asymptomatic HT occasionally need surgical intervention. Discomfort in swallowing and tightness in the neck are relieved after surgery. Thyroidectomy is safe to perform and has a low incidence of permanent complications. There was no associated malignancy in our series of HT.

A 50-year-old male patient presented with fever, epistaxis and multiple lymphadenopathy since 15 days. In the light of the above presentation a complete workup was initiated to exclude common conditions like tuberculosis, acquired immunodeficiency syndrome, lymphoid malignancy and sarcoidosis. After excluding common conditions a biopsy of cervical lymph node demonstrated reactive lymphadenitis with paracortical hyperplasia. Immunohistochemistry demonstrated double negative lymphocytes (CD4-, CD8-). A diagnosis of autoimmune lymphoproliferative disorder syndrome (ALPS) (probable) was made and patient was started on 1 mg/kg of steroids. Patient showed a dramatic improvement with respect to general wellbeing, fever and regression of lymphadenopathy. This entity of ALPS has been recently identified and classified; most of the reports are from the pediatric population. To the best of our knowledge ours is one of the few cases of this entity being reported in an adult patient from India.

Background : The pandemic of H1N1 2009 influenza has spread world over and low degree of virus transmission has continued in several regions of India. Aims : To assess the immunogenicity and safety of Pandemic Influenza (H1N1) 2009 Monovalent Vaccine in healthy adult Indian population. Settings and Design : Prospective, open label, multicentric, phase 2/3 clinical trial. Materials and Methods : Healthy adult Indian subjects belonging to either 18-59 years or ≥60 years age groups were enrolled and administered a single 0.5 ml (≥15 mcg of hemagglutinin antigen) dose of vaccine in the deltoid muscle. Anti-hemagglutinin antibody titer was assessed at baseline and 21 (±2) days after vaccination by Hemagglutination Inhibition (HI) test. Safety assessments were done for a period of 42 days. Statistical Analysis Used : Percentages of appropriate population with 95% confidence intervals calculated, log transformation of the data to calculate Geometric Mean Titers (GMTs) and chi-square test and student's t-test applied for significance testing. Results : 182/198 and 53/63 volunteers in age groups of 18-59 years and ≥60 years, respectively, achieved an HI titer ≥1 : 40 at Day 21 (91.9% [95% confidence interval: 88.1-95.7%] and 84.1% [75.1-93.2%]; P=0.072). Further, 171/198 and 50/63 volunteers in the respective age groups achieved seroconversion/four-fold increase in titer at Day 21 (86.4% [81.6-91.1%] and 79.4% [69.4-89.4%]; P=0.179). A significant rise of 22.6-fold [18.0-28.4] and 10.5-fold [7.4-15.0] was noted in GMT in the respective age groups (P<0.001 for both groups as compared to baseline). Nine vaccine-related adverse events were reported (3.4% incidence [1.2-5.6%]), which were of low severity only. Conclusions : Pandemic Influenza (H1N1) 2009 Monovalent Vaccine produces excellent immunogenic response with a good tolerability profile in adult Indian population.

Placental-based complications of pregnancy can be classified as acute and chronic. An example of acute placental complication is abruptio placenta. The chronic placental complications include pregnancy induced hypertension (PIH) and idiopathic Intrauterine growth restriction (IUGR). The fetus is at risk for perinatal complications in both acute and chronic conditions. Here we take a look at the natural history of the Doppler parameters in chronic conditions. The techniques used for assessing the fetal well-being include, clinical methods, biophysical tests, conventional ultrasonography, and fetal Doppler studies. Arterial Doppler studies are used to assess the well-being of the fetus and to determine the timing of delivery. However, arterial Dopplers predict only the subset of fetuses at risk of having perinatal complications. Venous Dopplers have been used to improve upon the prognostication. However, by the time the commonly used venous Doppler signs, that is, 'A' wave reversal in ductus venosus (DV) is present, the fetus is likely to be already compromised. The fetus tries to adapt to the environment of deprivation by making a series of changes in the umbilical artery circulation, cerebral circulation, and hepatic circulation. As a result of these adaptations, the fetus overcomes the state of chronic hypoxia. This article takes a look at these changes and also the effect of these adaptations. It is suggested that serial comparisons of the venous flow characteristics of the DV and inferior vena cava (IVC) can provide an early indication of the impending decompensation and can be used to predict the time the delivery.

Purpura fulminans is an acute illness characterized by rapidly progressive dermal vascular thrombosis, leading to hemorrhagic necrosis of the skin. Here, we describe the case of a healthy woman who developed acute disseminated intravascular coagulation (DIC) with purpura fulminans after intramuscular administration of a single dose of ketorolac. Review of literature showed only one case description of non-steroidal anti-inflammatory drug (diclofenac)-related purpura fulminans with DIC.

Endoscopic third ventriculostomy (ETV) has now been accepted widely as a safe procedure for treatment of non-communicating hydrocephalus. Despite its learning curve, most of the neurosurgeons have understood its technical details, benefits, and risks and have started to practice it to perfection. The benefit of shunt independence with minimal risks offers a remarkable advantage which has made this procedure widely popular. However, late closure of stoma leading to morbidity and even death has been reported off late. We report a case of a 7-year-old girl with hydrocephalus due to tectal glioma who deteriorated after 7 months following a successful procedure. She developed a cardio-respiratory arrest and was resuscitated with aspiration of cerebrospinal fluid from the ommaya reservoir kept during the primary surgery. Keeping all the patients under strict surveillance for stoma patency is mandatory and in addition, ommaya reservoir in certain high-risk patients may be a useful option for achieving quick ventricular access by medical and nonmedical personnel in case of deterioration. This case is the first reported case of acute deterioration after ETV from India. Previously, 14 such cases have been reported worldwide and only 2 of them have survived.

Neurologic complications are not uncommon in renal transplant recipients. Acute femoral neuropathy, lumbosacral plexopathy, and sciatic neuropathy have been reported after kidney transplantation probably due to perioperative nerve compression and ischemia. To the best of our knowledge, common peroneal nerve (CPN) palsy has not been described in the early postoperative period following renal transplantation. Also, mononeuropathy due to tacrolimus (TAC) therapy has not been described so far. We report a case of isolated CPN palsy presenting as unilateral foot drop following renal transplantation and that improved only after replacing TAC with cyclosporine.

Background : Suspected pulmonary thromboembolism (PTE) is a common presentation to acute medical units and can cause diagnostic difficulty. National guidelines on PTE management highlight the need for clinical probability assessment and D-dimer assays to ensure appropriate use of diagnostic imaging. D-dimers are used widely in UK hospitals, yet concern exists regarding their misuse. Aims : In this study we aimed to assess the impact of the introduction of D-dimer assays, combined with clinical probability assessment, for evaluation of suspected PTE in our unit. Materials and Methods : This was a prospective audit of all patients presenting with suspected PTE over two 12-week periods, exactly 1 year apart. D-dimers were introduced into our unit between these two periods. We recorded the clinical probability score, potential causes of false-positive D-dimer assay, diagnostic imaging result, patient outcome, admission rates, and length of inpatient stay. Statistical Analysis : Categorical variables were compared using a 2 x 2 chi-square test or Fisher's exact test. Groups were compared utilizing the two-sample t-test or Mann-Whitney U test. Results : A total of 190 patients were included in the study; 65% were female. PTE was confirmed in 8.4%. Patients in both audit periods were comparable with regard to suitability for D-dimer measurement. Following D-dimer introduction, 40 out of 110 patients in period 2 could be discharged directly from the emergency department. Of those admitted to hospital, the median length of stay was significantly reduced in period 2 (3 days in period 1 vs 1 day in period 2; P=0.0007). Use of diagnostic imaging was significantly reduced following the introduction of D-dimers (90% in period 1 vs 40% in period 2; P<0.0001). The positive diagnostic yield for PTE on CT pulmonary angiogram (CTPA) increased significantly from 10% in period 1 to 23% in period 2 (P=0.039). Conclusion : D-dimers must be used judiciously in the assessment of suspected PTE. Appropriate use of D-dimers can provide many benefits, including reductions in diagnostic imaging (and thus radiation exposure), admission rates, and length of inpatient stay.

Background : Indian patients with primary hyperparathyroidism (pHPT) usually present with a triad of advanced disease of bones, stones, and psychic moans. There are hardly any reports from India on the outcome of successful parathyroidectomy on psychiatric symptoms. Aims : To evaluate the outcome of parathyroidectomy on psychiatric symptoms in Indian patients with advanced pHPT. Settings and Design : Prospective study done in a tertiary care super-specialty hospital in northern India. Materials and Methods : Health surveys using parathyroid assessment of symptom score (PAS) and SF-36v2 were carried out, to evaluate the outcome of parathyroidectomy on the psychiatric symptoms of patients. The study included 42 patients of pHPT admitted between November 2007 and December 2009 (two years). Scoring was done preoperatively; and one week, three months, six months, and one year postoperatively. Statistical Analysis Used : SPSS 15 software and nonparametric tests (k Independent Sample test, Kruskal-Wallis H). Results : The mean preoperative PAS score was 430.87 ± 215.61 (range 40 - 880). Statistically significant reduction in scoring was observed postoperatively at one week (293.65 ± 118.31, P < 0.001), three months (109.44 ± 85.09, P < 0.015), six months (70.00 ± 71.65, P 1 < 0.05), and one year (60.10 ± 104.48, P < 0.02). Although the surgery scores for feeling irritability, forgetfulness, difficulty in getting out of chair, headache, and itchy skin did not reduce appreciably at one week, they later showed significant reduction. All other parameters showed significant reduction. The SF-36v2 TM survey also showed significant improvement on all scores except social functioning, while physical functioning improved only after one week. Conclusions : Indian patients with advanced pHPT, after a successful parathyroidectomy, showed significant improvement in their quality of life, as evaluated by the PAS and SF-36v2 systems.

We present a case of a 47-year-old female who presented with sicca symptoms since three months. As per the Revised International Classification Criteria for Sjögren's syndrome, patient was diagnosed as primary Sjögren's syndrome (SS). Patients with SS are known to have circulating monoclonal immunoglobulins. Serum electrophoresis revealed M band with serum gamma globulin concentration of 46 g/L. Bone marrow aspiration revealed 28% plasma cells. In absence of myeloma-related organ damage, a diagnosis of smouldering myeloma (MM) was made. Patient was treated with thalidomide and dexamethasone. Sicca symptoms resolved with anti-myeloma treatment. Although MM can occur as a complication of SS, MM can also rarely present as SS. In the present case, the short duration of sicca symptoms and response of these symptoms to anti-myeloma treatment support the diagnosis of MM presenting as SS. The present case highlights the importance of serum electrophoresis in patients presenting as SS.